Medical Wikipedia : The Medical Encyclopedia
It is a neurodegenerative disease that affects the brain, leading to impairment
of cognitive and behavioral function. It starts slowly and the disease process progresses over years
until symptoms are noticed. It accounts for 60-70% of cases of dementia. The
most common early symptom is usually found to be short term memory loss.
Alzheimer’s has become a serious health problem in the elderly demographic
in recent times. It was first described by Alzheimer in 1901. Over the last
decade, research on etiology and pharmacological treatment of Alzheimer’s
has been done in depth. Treatment focuses mainly on cholinergic therapy to
compensate for deficiency of Acetylcholine in the CNS.
1. First symptoms affect complex activities of daily living. Short term
memory loss is the main symptom. Other symptoms include problems in
attentiveness, planning, impairment in abstract thinking and semantic
memory. Apathy is the most persistent symptom that is observed early
and seen throughout the course of the disease.
2. The preclinical stage of this disease is termed Mild Cognitive
Impairment. It is a transitional stage between normal ageing and senile
dementia. MCI with memory loss as primary symptom is called amnestic
Early stage of Alzheimer’s disease
3. Early Stage: Early stage of Alzheimer’s disease sees progression of
learning and memory impairment to the point where it is definitively
diagnosed. Alzheimer’s affects the different memory capacities to
different extents. Episodic memory, Semantic memory and Implicit
memory is affected to a lesser extent than memory of new information.
Apraxia (difficulty in performing fine motor movements) and Agnosia are
noticed to a lesser extent.
Middle stage of Alzheimer’s disease
4. Middle Stage: Ability of subject to perform certain activities of daily
living become increasingly impaired. Behavioral and Neuropsychiatric
changes become more prevalent while language skills and fluency
declines significantly. Long term memory is first impaired in this stage.
Appearance of emotional instability, unpremeditated aggression,
irritability and wandering is seen. Sundown Syndrome, which is
characterized by increased confusion and restlessness is observed as
Final stage of Alzheimer’s disease
5. Final Stage: This is the final stage of Alzheimer’s. The subject is
completely dependent on caretakers to perform activities of daily living.
Complete loss of speech along with extreme apathy and
exhaustion is noticed. The cause of death is due to external infections like
The major neuropathological features of Alzheimer’s Disease is mostly
senile plaques and neurofibrillary tangles. The senile plaques seem to develop
first in brain areas associated with cognition and spread to other cortical areas
as the disease progresses. The senile plaques consist of insoluble deposits of
amyloid p-peptide (Amyloid beta), a fragment of the amyloid precursor protein
(APP). Amyloid beta peptide is generated from APP by two consecutive
cleavage events: proteolytic activity by β-secretase generates one end of the
Amyloid p-peptide, and γ-secretase generates the other end, also by
Formation of neurofibrillary tangles is attributed to the accumulation of tau
protein, which is involved in maintaining stability of microtubules in axons of
neurons. Tau protein undergoes phosphorylation to stabilize the microtubules
in physiological conditions. In Alzheimer’s disease, Tau protein undergoes
change to become hyperphosphorylated. This leads to formation of new pairs
of microtubules linked together, creating the neurofibrillary tangles.
The mechanism of formation of amyloid plaques leading to Alzheimer’s disease
is not known well. A certain hypothesis says that the accumulation of beta
amyloid leads to neuronal degeneration. This occurs by disrupting the calcium
homeostasis of neurons, which in turn leads to release of cytochrome c from
mitochondria through formation of Mitochondrial Permeability Transition Pore
(MPTP). This triggers the intrinsic pathway of apoptosis by formation of
apoptosome complex by cytochrome c with other pro-apoptotic factors,
activating the caspase cascade, which mediates the process of apoptosis.
This cellular degeneration leads to destruction of cholinergic neurons, which
results in the pathology of Alzheimer’s disease. Inflammation and cytokines are
also said to play a role in the pathology of Alzheimer’s disease.
1. Psychosocial treatment
Environmental manipulation, family support, and prevention of other medical
comorbidities can improve functioning of patients. Changes in routine life like
daily remainders for performing daily activities and minimal focus on other
activities, concentrating on maintaining satiety, hydration, nutrition and
2. Pharmacological treatment:
Administration of cognitive enhancers, antidepressants, antipsychotics, mood
stabilizers and hypnotics is followed to treat neuropsychiatric symptoms.
Treatment of cognitive disturbance
3. Treatment of cognitive disturbance:
Cholinesterase inhibitors, estrogen replacement therapy, anti-inflammatory
drugs and antioxidants like vitamin E and selenium in selegiline. Abrupt decline
in estrogen in post-menopausal women is one of the main reasons for
increased risk of Alzheimer’s disease in elderly women, as estrogen is shown to
play an important role in brain development and neuronal plasticity.
Treatment of behavioral disturbances
4. Treatment of behavioral disturbances:
Reversible monoamine oxidase inhibitors like brofaromine and moclobemide
are helpful in dealing with depression and dementia. Antidepressants like
fluoxetine, paroxetine and fluvoxamine are helpful in treating depression.
Risperidone is used as an antipsychotic drug to treat psychosis.